Coric disrupted Nishikori’s run of form by winning both tiebreaks with a solid serve in one hour and 59 minutes.
The third player to secure a spot in the semi-finals after seeded players Stefanos Tsitsipas, and Andrey Rublev, Borna Coric is making a flawless appearance at the ATP 500 event.
The world No. 26 begun his run in Rotterdam defeating wild card Botic van de Zandschulp 6-4, 7-6 (4).
Following a top performance against Dusan Lajovic the 24-year-old - dropped only five games during the encounter, sealed the match with a victory in straight sets 6-3, 6-2, securing a spot in the last eight.
With two ATP titles under his belt - Marrakech, and Halle - Coric faced Kei Nishikori for the second time in his career, achieving his first triumph over the Japanese tennis player.
The 31-year-old - who is making a comeback after recovering from surgery on his right elbow, became the first player to qualify to the quarter-finals, producing a solid campaign throughout the tournament.
Nishikori met Canadian Felix Auger-Aliassime in the first round of the competition, defeating the 20-year-old in straight sets 7-6 (4), 6-1 - his first victory in five months.
Playing for the second round in Rotterdam, world No. 45 hit the Center Court to face Australian Alex de Minaur, earning victory 6-3, 2-6, 7-5.
Even with Friday’s loss, Nishikori says farewell to Rotterdam, having fought until the end, warming up for the rest of the season, which has only begun last month.
The Croat next rival is qualifier Marton Fucsovics, who beat Tommy Paul 6-2, 6-3.
The Hungarian qualified for the event, outlasting Frenchmen Arthur Rinderknech 6-2, 6-4 and Pierre-Hugues Herbert 6-4, 6-3.
The 29-year-old rallied past Reilly Opelka 7-6 (2), 6 (4)-7, 7-6 (4).
On Thursday, playing the round of 16, he moved past Alejandro Davidovich Fokina 6-3, 6-2 to reach the last eight, earning victory over Paul.
Coric and Fucsovics will play at Center Court on Saturday.